Reflection detection type measurement apparatus and method for skin autofluorescence

ABSTRACT

Provided is a reflection detection type measurement method for skin fluorescence. The method includes: irradiating excitation light on a measurement target; detecting a reflected light and a skin fluorescence generated from the measurement target due to the excitation light; irradiating light with a wavelength range of the skin fluorescence on the measurement target; detecting a reflected light generated from the measurement target due to the light with a wavelength range of the skin fluorescence; and calculating a skin fluorescence value of the measurement target by correcting a calculation based on the detected reflected light and skin fluorescence.

CROSS-REFERENCE TO PRIOR APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 13/845,792, filed on Mar. 18, 2013, which in turn claims under35 U.S.C. §119(a) the benefit of Korean Patent Application No.10-2012-0028675 filed Mar. 21, 2012 and Korean Patent Application No.10-2012-0074250 filed Jul. 9, 2012, and Korean Patent Application No.10-2013-0009774 filed Jan. 29, 2013, the entire contents of which areincorporated herein by reference.

TECHNICAL FIELD

This application relates to a skin autofluorescence measuring apparatusand method for diagnosing various diseases such as diabetes, bymeasuring autofluorescence of the skin from Advanced GlycationEnd-products (AGEs) accumulated in the skin.

BACKGROUND

Recently, various apparatuses using light for the purpose of diagnosisand treatment of diseases are being developed. Particularly, variousapparatuses for diagnosing diseases using skin autofluorescence emittingout of the skin by excitation light irradiated from a light source arebeing developed and used.

The autofluorescence is the emission of light from the skin afterexcitation light is absorbed into the skin. Since having the biometricdata inside the skin, the autofluorescence serves as a biomarker ofdiseases, and enables checking of the damage of physiological state ofall body organs by a non-invasive method.

For example, Advanced Glycation End-products (AGEs) are formed viaglycoxidation of proteins in human body as a result of Maillard reactionwhich impairs the functioning of many proteins. In general, exposure tocardiac risk factors such as smoking, intake of high fatty acidcontaining foods, hypercholesterolemia, and oxidative stress due toacute diseases such as sepsis lead to generation of AGEs. Thus producedAGEs are slowly decomposed and accumulated over a long period of time inthe body. An increase in AGEs production is associated with the progressof chronic diseases such as atherosclerosis. With the aging process,AGEs tend to accumulate in the body throughout a person's life.

During the continuation of hyperglycemia, continual reactions ofnon-enzymatic protein glycation and glycoxidation occur, and thus AGEs,i.e., a complex of irreversible glycogen and protein, are formed.Accumulation of AGEs rapidly progresses in patients suffering fromdiabetes, renal failure and cardiovascular diseases. AGEs areaccumulated in various tissues including skin. AGEs have thecharacteristics of irradiating autofluorescence (AF) at a range of bluespectrum (peak near about 440 nm) by excitation light irradiation of theUV range (peak near about 370 nm)

AGEs can be used as a bio marker regarding a series of diseases, andenable to evaluate physiological damages of the whole body organs bymeasuring autofluorescence of skin using a non-invasive method. That is,AGEs can predict long-term complications in age-related diseases. Inparticular, the quantity of skin autofluorescence increases in patientssuffering from diabetes and renal failure, and relates to the progressof vascular complications and Coronary Heart Disease (CHD). The AGEaccumulation can be measured by skin autofluorescence by a non-invasivemethod, a non-invasive clinical tool useful for the risk evaluation oflong-term vascular complications under environments associated with theaccumulation of AGEs and diabetes.

US Patent Application Publication No. 2004-186363 (hereinafter, referredto as Reference 1) discloses technology of evaluating AGEs by measuringskin fluorescence near the forearm of a patient as a method andapparatus that are proposed for AGE evaluation using skinautofluorescence measurement.

In Reference 1, an excitation light source is a blacklight fluorescenttube that emits light in a UV wavelength range of about 300 nm to about420 nm. The collection and recording of light are performed by anoptical fiber spectrometer. In order to increase a measurement area, theend surface of an optical fiber is disposed apart from a transparentwindow of the apparatus by a certain distance (d is about 5 mm to about9 mm). In order to reduce an influence of light reflected from skin, theoptical fiber is disposed oblique to the surface of the window at about45 degrees.

Specifically, in Reference 1, the end surface of the optical fiber forcollecting light is disposed as distant as possible from a target spot.In this case, the area of the target spot to be measured is about 0.4cm2.

However, there is a limitation in the above method that a fluorescentsignal that is collected is considerably reduced as the measurementdistance (d) increases to increase the measurement area of the targetspot. Accordingly, in Reference 1 according to a related art, thereliability of data detection may be reduced due to a limitation of thesize of the skin area that can be measured. Particularly, such anaccuracy limitation is considerably represented in parts such as moles,vessels, and wounds that are heterogeneous spots of skin.

Meanwhile, US Patent Application Publication No. 2008-103373(hereinafter, referred to as Reference 2) discloses an apparatus formeasuring AGEs to perform a screen test of a diabetic. Similarly toReference 1, the apparatus disclosed in Reference 2 includes an opticalfiber spectrometer to perform fluorescence measurement on the forearmskin. However, unlike in Reference 1, optical fiber probes are providedin a form of bundle including multiple branches.

In the apparatus of Reference 2, UV light and blue light emitting fromlight-emitting diodes are irradiated on the forearm of a subject throughoptical fiber probes, and skin fluorescence and diffusion reflectionlight emitting therefrom are collected through the probes. The collectedlight is wavelength-dispersed in a spectrometer, and then detected by alinear array detector. Two branches (illumination fibers; channel 1 andchannel 2) of the optical fiber probe serve to irradiate light on atarget spot, and a third branch (collection fibers) delivers light fromthe target to a multi-channel spectrometer. The end surface of a tissueinterface, where the branch bundles of the optical fiber probes arecombined, becomes in contact with skin to be irradiated.

Light from a white light LED is emitted from one branch of the opticalfiber probe for reflected light spectrum measurement, and light from anappropriate LED among LEDs emitting light of ultraviolet to a blue lightspectrum range is emitted from another branch of the optical fiber probevia a switching apparatus. Various wavelengths can be selected to selectoptimal fluorescence excitation conditions. The reflected light spectrummeasurement is used to detect autofluorescence generated due to melaninand hemoglobin and compensate for the measurement result. Respectiveoptical fibers are disposed in the optical fiber bundle by a certainsequence. Optical fibers from three branches of the optical fiber bundleare sequentially disposed in a mosaic pattern at an interval of b=0.5mm.

In Reference 2, since light is irradiated on the forearm of a subjectthrough an optical fiber probe, the optical fiber probe is included asan optical-transmission medium.

However, the optical fiber probe has a limitation in delivery loss foreach specific wavelength which occurs according to the mediumcharacteristics of optical fibers. Further, additional optical designand optical system are required for incidence light generated from alight source based on a total reflection condition of optical fiber.

Additionally, since both apparatuses disclosed in References 1 and 2include optical fibers in a light-receiving unit that receives light,there is an inherent limitation in the optical fiber probe of thelight-receiving unit. Since References 1 and 2 are configured to use anoptical fiber spectrometer and a linear array detector, there is alimitation in that the autofluorescence signal wavelength of AGE becomesrelatively smaller in a detection area that is occupied by the lineararray detector. Accordingly, a detected fluorescence signal isdispersed, and the light intensity of a wavelength to be detected by thelinear array detector becomes relatively smaller. Also, due to theoptical fiber probe and optical fiber spectrometer, it is difficult tominimize facilities.

On the other hand, the diagnosis apparatuses disclosed in References 1and 2 have a limitation in that it is impossible to diagnose diseasessuch as a diabetic foot accompanied by diabetes.

The diabetic foot is a sort of serious complications that incur adiabetic foot ulcer and a lower leg amputation according to the progressof diabetes. It is reported that the diabetic foot occurs in about 15%of all patients with diabetes and about 40% to about 60% of all lowerleg amputation patients are diabetic patients. The diabetic foot ulceris a cause in about 80% or more of all lower leg amputation patients.About 90% or more of patients with the diabetic foot can be curedwithout amputation when they are appropriately treated at an earlystage. The autofluorescence measurement test can be used for an earlydiagnosis of the diabetic foot. At an early stage of the diabetic foot,the diabetic foot usually occurs in one foot before its progress in theother foot. Accordingly, the early diagnosis of the diabetic foot usingthe fluorescence test can be performed by comparing and evaluating thefluorescence degree of skin of the symmetrical foot part. Therefore, forearly diagnosis of diseases such as diabetic foot together with typicaldiabetes, there is a need for the development of an apparatus thatenables a selective diagnosis on body parts to be measured.

Particularly, for implementing the selective diagnosis apparatus, theminiaturization and the mobility of the apparatus has to be firstprepared. Accordingly, the efficiency of light irradiation andfluorescence detection in the apparatus is needed.

Meanwhile, although such a selective diagnosis is performed on bodyparts, the intensity of the fluorescence generated from the skin isaffected by the light scattering and absorption occurring inside theskin as well as fluorescence substances included in the skin.

Therefore, it is very important to improve the efficiency of the lightirradiation and the fluorescence detection and reduce a measurementerror due to the light scattering and absorption inside the skin inorder to achieve an exact diagnosis on selective diagnosis parts formore clearly discriminating between persons with diseases and personswithout diseases.

The above information disclosed in this Background section is only forenhancement of understanding of the background of the invention andtherefore it may contain information that does not form the prior artthat is already known in this country to a person of ordinary skill inthe art.

SUMMARY

An embodiment of the present invention provides a reflection detectiontype measurement apparatus for skin fluorescence, which can simplycorrect a measurement error of skin fluorescence due to light scatteringand absorption generated in the skin and reflected light of irradiationlight from the skin surface, in measuring skin fluorescence.

An embodiment of the present invention also provides a reflectiondetection type measurement apparatus for skin fluorescence, which canincrease a diagnosis possibility of diseases such as diabetes by exactlyevaluating diagnosis factors such as AGEs from corrected skinfluorescence values.

An embodiment of the present invention also provides a reflectiondetection type measurement apparatus for skin fluorescence, which canimprove the optical efficiency by efficiently concentrating light from alight source on the skin tissue and minimizing the specular reflectionfrom the surface of the skin tissue, in measuring skin fluorescence.

An embodiment of the present invention also provides a reflectiondetection type measurement apparatus for skin fluorescence, which canimprove the optical concentration and the optical uniformity byuniformly concentrating light irradiated from a light source to ameasurement target.

An embodiment of the present invention also provides a reflectiondetection type measurement apparatus for skin fluorescence, in which anoptical system and a light source system can be simply configured toconveniently perform a diagnosis process.

In accordance with an aspect of the present invention, a reflectiondetection type measurement method for skin fluorescence includes:irradiating excitation light on a measurement target; detecting areflected light and a skin fluorescence generated from the measurementtarget due to the excitation light; irradiating light with a wavelengthrange of the skin fluorescence on the measurement target; detecting areflected light generated from the measurement target due to the lightwith a wavelength range of the skin fluorescence; and calculating a skinfluorescence value of the measurement target by correcting a calculationbased on the detected reflected light and skin fluorescence.

A dark time is maintained for a certain time before irradiating theexcitation light on the measurement target, and a dark signal value ofthe measurement target compensates the skin fluorescence value duringthe dark time.

A wavelength of the excitation light has a range of 370±20 nm.

A wavelength of the skin fluorescence has a range of 440±20 nm.

The excitation light and the skin fluorescence are irradiated on thesame area of the measurement target.

The excitation light is irradiated on the measurement target for a firsttime, and the skin fluorescence is irradiated on the measurement targetfor a second time after the first time.

Detecting a reflected light and a skin fluorescence generated from themeasurement target due to the excitation light comprises detecting lightwith a specific wavelength range of the reflected light and the skinfluorescence.

A wavelength range of the reflected light is smaller than a wavelengthrange of the skin fluorescence.

In accordance with another aspect of the present invention, a reflectiondetection type measurement method for skin fluorescence includes:detecting light with a first wavelength range and light with a secondwavelength range generated from a measurement target by irradiating thelight with a first wavelength range on the measurement target; detectingthe light with a second wavelength range generated from the measurementtarget by irradiating the light with a second wavelength range on themeasurement target; and calculating a skin fluorescence value of themeasurement target by correcting a calculation based on the detectedlight with a first wavelength range and light with a second wavelengthrange.

A reflection detection type measurement method for skin fluorescencefurther includes maintaining a certain dark time before irradiating thelight with a first wavelength range on the measurement target.

A reflection detection type measurement method for skin fluorescencefurther includes maintaining a certain dark time before irradiating thelight with a second wavelength range on the measurement target.

In accordance with another aspect of the present invention, a reflectiondetection type measurement apparatus for skin fluorescence includes: afirst light source irradiating light with a first wavelength range on ameasurement target; a second light source irradiating light with asecond wavelength range on the measurement target; a first opticaldetector detecting the light with a first wavelength range generatedfrom the measurement target by the light of the first light source; asecond optical detector detecting the light with a first wavelengthrange generated from the measurement target by the light of the firstlight source, and detecting the light with a second wavelength rangegenerated from the measurement target by the light of the second lightsource; and a light source switching controller controlling a turnedon/off of the first light source and the second light source.

The light with a second wavelength range is longer than the light with afirst wavelength range.

The light source switching controller turns off the first light sourceand the second light source so as to maintain a dark time for a certaintime before irradiating the light of the first light source.

The light source switching controller turns off the first light sourceand the second light source so as to maintain a dark time for a certaintime before irradiating the light of the second light source.

The first optical detector is turned off while the second opticaldetector detects the light generated from the measurement target due tothe light with a second wavelength range.

The first optical detector and the second optical detector are turned onduring a dark time maintained for a certain time before irradiating thelight of the first light source.

The first optical detector and the second optical detector are turned onduring a dark time maintained for a certain time before irradiating thelight of the second light source.

The first wavelength range has a range of 370±20 nm.

The second wavelength range has a range of 440±20 nm.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other features of the present invention will now bedescribed in detail with reference to certain exemplary embodimentsthereof illustrated the accompanying drawings which are givenhereinbelow by way of illustration only, and thus are not limitative ofthe present invention, and wherein:

FIG. 1 is a graph illustrating the intensities of light inputted from alight source and light detected by an optical detector which are shownaccording to time to explain the measurement principle of a reflectiondetection type measurement apparatus for skin fluorescence according toan embodiment of the present invention;

FIG. 2 is a view illustrating a reflection detection type measurementapparatus for skin fluorescence according to an embodiment of thepresent invention;

FIG. 3 is a view illustrating an exemplary arrangement of light sourcesand optical detectors when there is no gap between the light sources andthe optical detectors and a target skin in a reflection detection typemeasurement apparatus for skin fluorescence according to an embodimentof the present invention;

FIG. 4 is a view illustrating an exemplary arrangement of light sourcesand optical detectors when there is a gap between the light sources andthe optical detectors and a target skin in a reflection detection typemeasurement apparatus for skin fluorescence according to an embodimentof the present invention;

FIG. 5 is a view illustrating an optical prism and an optical connectorin a reflection detection type measurement apparatus for skinfluorescence according to an embodiment of the present invention;

FIGS. 6 through 10 are views illustrating an optical prism and anoptical connector in a reflection detection type measurement apparatusfor skin fluorescence according to an embodiment of the presentinvention;

FIG. 11 is a view illustrating a reflection detection type measurementfor skin fluorescence according to an embodiment of the presentinvention, which is configured to include a housing equipped with twolight sources and two optical detectors;

FIG. 12 is a plan view illustrating a pyramidal holder in which lightsources and optical detectors are installed in a reflection detectionpyramidal measurement apparatus for skin fluorescence according to anembodiment of the present invention;

FIGS. 13 through 15 are exploded views illustrating a pyramidalmeasurement module of a reflection detection pyramidal measurementapparatus for skin fluorescence according to an embodiment of thepresent invention; and

FIG. 16 is a view illustrating an optical attenuation filter in areflection detection pyramidal measurement apparatus for skinfluorescence according to an embodiment of the present invention.

It should be understood that the appended drawings are not necessarilyto scale, presenting a somewhat simplified representation of variouspreferred features illustrative of the basic principles of theinvention. The specific design features of the present invention asdisclosed herein, including, for example, specific dimensions,orientations, locations, and shapes will be determined in part by theparticular intended application and use environment.

In the figures, reference numbers refer to the same or equivalent partsof the present invention throughout the several figures of the drawing.

DETAILED DESCRIPTION

Hereinafter reference will now be made in detail to various embodimentsof the present invention, examples of which are illustrated in theaccompanying drawings and described below. While the invention will bedescribed in conjunction with exemplary embodiments, it will beunderstood that present description is not intended to limit theinvention to those exemplary embodiments. On the contrary, the inventionis intended to cover not only the exemplary embodiments, but alsovarious alternatives, modifications, equivalents and other embodiments,which may be included within the spirit and scope of the invention asdefined by the appended claims.

The above and other features of the invention are discussed infra.

According to an embodiment of the present invention relates to a skinfluorescence measurement apparatus for irradiating excitation light onthe skin and measuring skin fluorescence generated by the excitationlight for the purpose of diagnosis of diseases such as diabetes.Particularly, it provides a reflection detection type measurementapparatus for skin fluorescence, which can exactly measure skinfluorescence detected at a location where reflected light is projectedamong skin fluorescence scattered and emitted from inside of the skindue to light irradiated on the skin.

For this, a sequential measurement may be performed on a target to bediagnosed and a reference sample, and information obtained from thetarget may be compared with information obtained by the reference sampleto remove an individual deviation that the target has, while a lightsource and an optical detector may be sequentially turned on/offaccording to certain conditions required in the above process. Thus,provided is a reflection detection type measurement apparatus for skinfluorescence that can provide a corrected skin fluorescence value.

Hereinafter, exemplary embodiments of a reflection detection typemeasurement apparatus for skin fluorescence will be described in detailwith reference to the accompanying drawings.

It is necessary to select a skin target for measurement of fluorescencegenerated on the skin and consider factors that affect the measuredfluorescence. The measured fluorescence may depend on light scatteringand absorption occurring inside the skin even when specular reflectionoccurring on the skin surface is removed, as well as fluorescentsubstances included in the skin. Particularly, it is necessary tocorrect measured fluorescence values in consideration of influences oflight absorption and scattering in the fluorescence wavelength generatedin fluorescent substances and the excitation light wavelength irradiatedto excite fluorescent substances.

Accordingly, the following empirical Equation (1) may be considered toreduce the influence of optical factors on the fluorescent intensity.

AF_(corr)=AF/(R ₁ ^(k1) R ₂ ^(k2))  (1)

Here, a corrected fluorescence value AF_(corr) may be obtained bydividing a measured fluorescence value AF by an excitation diffusionreflection light R1 and a diffusion reflection light R2 of emission inthe fluorescent wavelength range. The two diffusion reflection lightvalues may be adjusted by exponents k1 and k2 without a degree.

Equation (1) may be used to obtain the corrected skin fluorescencevalue, and concrete values may be introduced to obtain the correctedskin fluorescence value through an actual test.

I(λ2,t1) Inherent fluorescence (skin fluorescence) signal value of skintissue

I(λ1,t1): Reflected light signal value of skin tissue in excitationlight wavelength

I(λ2,t2): Reflected light signal value of skin tissue in emission lightwavelength

k1, k2: Exponents of correction function with respect to excitationlight and emission light wavelength

The corrected skin fluorescence value that is newly induced may beexpressed as Equation (2).

AF_(tissue) =[I(λ2,t1]/[I(λ1,t1)^(k1) I(λ2,t2)^(k2) ];k1,k2<1  (2)

where AF_(tissue) is a correction signal of an inherent fluorescence ofa skin tissue.

The light measurement may be periodically performed at different timeintervals t1 and t2. The measurement results may be averaged to increasethe accuracy. The measured values may be recorded in a form of timediagram to trace the variation at an appropriate time.

Meanwhile, correction of deviations depending on equipment andcorrection measurement for a comparison between the results obtainedfrom different samples may be needed. Accordingly, in the presentinvention, the equal measurement may be performed by introducingreference samples together with the measurement of the target skintissue. In order to increase the measurement accuracy, the fluorescenceintensity I0(λ2, t1) and the reflected light signal values I0(λ1, t1)and I0(λ2, t2) in the excitation light and the emission light may besimilar to the optical characteristics of the skin.

The signal values generated in the measurement process of the introducedreference sample may be expressed as follows similarly to those for thetarget skin tissue.

I0(λ2,t1): Inherent fluorescence signal value of reference sample.

I0(λ1,t1): Reflected light signal value of reference sample inexcitation light wavelength.

I0(λ2,t2): Reflected light signal value of reference sample in emissionlight wavelength.

The signals obtained from the reference samples may be processed byEquation (3) similarly to Equation (2).

AF_(reference) =[I ₀(λ2,t1)]/[I ₀(λ1,t1)^(k1) I ₀(λ2,t2)^(k2)]  (3)

A result obtained by dividing AF_(tissue) by AF_(reference) may benormalized, and a finally corrected inherent fluorescence value may beexpressed as Equation (4).

AF_(corr) =K(AF_(tissue)/AF_(reference))  (4)

AF_(corr) =K[I(λ2,t1)/I ₀(λ2,t1)]/{[I(λ1,t1)/I ₀(λ1,t1)]^(k1)[I(λ2,t2)/I ₀(λ2,t2)]}^(k2)  (5)

where K is a ratio coefficient that considers the features of the usedreference samples.

Equation (5) may be simplified as Equation (6)

AF_(corr) =K[I(λ2,t1)/I ₀(λ2,t1)]/{[R(λ1)]^(k1) [R(λ2)]}^(k2)  (6)

R(λ1)=I(λ1,t1)/I0(λ1,t1): Diffuse reflection coefficient in excitationwavelength.

R(λ2)=I(λ2,t2)/I0(λ2,t2): Diffuse reflection coefficient in emissionwavelength.

Thus, regarding the reflection detection type measurement apparatus ofskin fluorescence according to the embodiment of the present invention,the corrected skin fluorescence values may be calculated by the aboveoperation processes.

In this regard, the principle proposed for the measurement will bedescribed in detail with reference to FIG. 1.

FIG. 1 is a graph illustrating the intensities of light inputted from alight source and light detected by an optical detector which are shownaccording to time to explain the measurement principle of a reflectiondetection type measurement apparatus for skin fluorescence according toan embodiment of the present invention, and FIG. 2 is a viewillustrating a reflection detection type measurement apparatus for skinfluorescence according to an embodiment of the present invention. Basedon FIG. 1 and FIG. 2, first, as shown in FIG. 1, in the reflectiondetection type measurement apparatus for skin fluorescence, themeasurement may be successively performed under a first condition inwhich light corresponding to a wavelength range (first wavelength λ1) ofexcitation light is irradiated as an input, and a second condition inwhich light corresponding to a wavelength range (second wavelength λ2)of skin fluorescence generated by the excitation light is irradiatedwhile being separated from each other in time.

The wavelength range of the irradiation light corresponding to the firstand second conditions may be selectively configured according to theskin fluorescence to be detected. For example, considering that the skinfluorescence is detected with respect to AGE in an exemplary embodiment,light with the first wave length of 370 nm±20 nm may be used as theexcitation light for the fluorescence excitation under the firstcondition, and light with the second wave length of 440 nm±20 nmcorresponding to the wavelength of the skin fluorescence with respect toAGE may be selectively used under the second condition.

That is, as shown in FIG. 2, the measurement may be performed using ameasurement scanner 100 including light sources 111 and 112 for emittingtwo different wavelengths of light and an optical detector 121, 122 fordetecting two different wavelengths of light. The measurement may beperformed by contacting the measurement scanner 100 with the skin tissuecorresponding to a measurement target in the diagnosis observanceprocess or the reference sample in the correction process.

In regard to the measurement process, FIG. 1A shows an operating timediagram showing the respective light sources with respect to twodifferent wavelengths operate while being separated from each other intime. In this case, light φ(λ1, t1) irradiated from a first light source111 that is an excitation light source may be configured to exist in adifferent and uncrossed time from light φ(λ2, t2) irradiated from asecond light source 112 that is a reference light source of differentwavelength range.

Meanwhile, FIG. 1B shows an operating time diagram with respect to twooptical detectors. In the same time while light φ(λ1,t1) is beingradiated from the first light source 111, two signals may be generatedwith respect to the excited skin fluorescence and the reflected light.Two signals generated in the excitation light wavelength may be areflected light signal I(λ1,t1) and an excited fluorescence signal I(λ2,t1).

Meanwhile, only a single signal may be generated in a time when lightφ(λ2,t2) is irradiated from the second light source 112. The signalgenerated by the second light source 112 may be only a reflected lightsignal I(λ2,t2) in the wavelength range of the irradiated light.

As shown in FIG. 1, in the reflection detection type measurementapparatus for skin fluorescence according to an embodiment of thepresent invention, the light irradiation of the first light source 111and the light irradiation of the second light source 112 may besequentially performed on the measurement target T while being separatedfrom each other in time. In this case, the signals detected from theoptical detector may be collected upon each light irradiation, and thenmay be calculated using the above equations to output the corrected skinfluorescence value.

FIG. 2 is a view illustrating a reflection detection type measurementapparatus for skin fluorescence according to an embodiment of thepresent invention, which is implemented by the measurement principledescribed above.

As shown in FIG. 2, the reflection detection type measurement apparatusfor skin fluorescence according to an embodiment of the presentinvention may include a measurement scanner 100 that irradiatesexcitation light on the skin and detects skin fluorescence, and a mainbody 200 that is connected to the measurement scanner 100 and analyzesdata detected by the measurement scanner 100 to display the data.

However, it will be only an exemplary configuration that the measurementscanner 100 and the main body 200 are configured to be separated fromeach other. Accordingly, if necessary, the reflection detection typemeasurement apparatus for skin fluorescence may be manufactured in aform of a single sensor without a separate main body, or may furtherinclude other components connected thereto.

The reflection detection type measurement apparatus for skinfluorescence according to an embodiment of the present invention may beconfigured to include a light source 111, 112 and an optical detector121, 122 to irradiate light on a target to be measured and detect skinfluorescence generated by the irradiated light.

In an embodiment of the present invention, in order to provide exactskin fluorescence values by correcting the detected skin fluorescencevalues, the reflection detection type measurement apparatus for skinfluorescence may include two light sources that irradiate differentwavelengths of light and two optical detectors that can detect differentwavelengths of reflected light and skin fluorescence generated by thetwo irradiation lights.

Specifically, the two light sources may include the first light source111 that emits light corresponding to the wavelength range (firstwavelength λ1) of the excitation light and the second light source 112that emits light corresponding to the wavelength range (secondwavelength λ2) of skin fluorescence generated by a target inside of ameasurement object due to the excitation light. The two opticaldetectors may include a first optical detector 121 for detectingreflected light λ1 reflected from the measurement object by theexcitation light emitted from the first light source 111 and a secondoptical detector 122 for detecting the skin fluorescence λ2 emitted fromthe target inside of the measurement object due to the excitation lightand the reflected light λ2 reflected from the measurement object by thereflected light from the second light source 112.

Therefore, the two light sources and optical detectors may be configuredto simultaneously detect the reflected light and the skin fluorescence.For example, the two light sources and optical detectors may be disposedat one end of the measurement scanner 100, and may be close to eachother so as to irradiate light on the measurement target T and detectthe reflected light.

In this case, light may be irradiated on the same area of the firstlight source 111 and the second light source 112, and the first opticaldetector 121 and the second optical detector 122 may be disposed todetect light generated from the same area of the measurement target. Iflight is irradiated on an area other than the same area of themeasurement object, it is difficult to obtain an accurate result valuewhen calculation for measuring the skin fluorescence is corrected. Inaddition, it is preferable that the same area of the measurement objectis set as a local area. If the same area of the measurement object isset as a broad area, it is difficult to expect accurate result valuebecause it is actually obtained through a complicated process whencalculation is corrected based on the light detection in a correspondingarea, and an additional component for complicated calculation isrequired and cost is increased.

In addition, the first optical detector 121 and the second opticaldetector 122 may difficult to detect an actually necessary light signalvalue due to a generated noise when the excitation light or the skinfluorescence generated from the measurement object is totally reflectedfrom the measurement object, and an error of necessary light signalvalue may be generated due to noise. Accordingly, the first opticaldetector 121 should be disposed in an area except for the totalreflection area to which the excitation light of the first light sourceis reflected after irradiating to the measurement target. In addition,it is preferable that the second optical detector 122 is also disposedin an area except for the total reflection area to which the excitationlight of the first light source and the light of the second light sourceare reflected after irradiating to the measurement target.

In an exemplary embodiment of the present invention, in order to detectthe skin fluorescence with respect to AGE, light with the firstwavelength of 370 nm±20 nm may be used as excitation light forfluorescence excitation, and light with the second wavelength of 440nm±20 nm corresponding to the wavelength of the skin fluorescence withrespect to AGE may be used as the reflected light.

That is, it is preferable that light of a wavelength range of skinfluorescence generated from the measurement target by the excitationlight of the first light source may be used as the light of the secondlight source.

In this case, the first light source 111 may include a light emittingdiode that irradiates light of the first wavelength range, 370 nm±20 nm.The second light source 112 may include a light emitting diode thatirradiates light of the second wavelength range, 440 nm±20 nm. Inaddition, the first optical detector 121 may include a photodiode thatdetects light of the first wavelength range, and the second opticaldetector 122 may include a photodiode that detects light of the secondwavelength range.

In an exemplary embodiment of the present invention, it was describedthat the first light source 111 and the second light source 112 havewavelength ranges of 370 nm±20 nm and 440 nm±20 nm. However, the lightsource may have a wavelength range corresponding to the target whenreaction conditions are different depending on the target to be measuredinside of the skin.

Meanwhile, the reflection detection type measurement apparatus for skinfluorescence according to an embodiment of the present invention mayfurther include a light source switching control unit 230 forcontrolling turning on/off of the first and second light sources 111 and112. More preferably, the reflection detection type measurementapparatus for skin fluorescence may further include an optical detectorswitching control unit 240 for controlling turning on/off of the firstand second optical detectors 121 and 122.

The light source switching control unit 230 and the optical detectorswitching control unit 240 may control switching such that the lightsources and the optical detectors can exactly operate according to thedetection conditions of the skin fluorescence and the reflected light inorder to exactly calculate the skin fluorescence values.

The light source switching control unit 230 may be configured to turn onor off the light sources according to the light irradiation conditionsof the reflection detection type measurement apparatus for skinfluorescence. For example, under the first condition in which excitationlight λ1 is irradiated on the measurement target, the second lightsource 112 may be turned off and the first light source 111 may beturned on, controlling switching of the light sources such that only thefirst light source 111 irradiates light of a first wavelength range. Onthe other hand, under the second condition in which the reflected lightλ2 of a different wavelength range from the excitation light isirradiated on the measurement target, the first light source 111 may beturned off and the second light source 112 may be turned on such thatlight of a second wavelength range is irradiated from only the secondling source 112.

That is, the light source switching control unit 230 may controlswitching of the first light source 111 and the second light source 112such that the first light source 111 and the second light source 112 areturned on in a different time.

Similarly, the optical detector switching control unit 240 may beconfigured to control turning on/off of the optical detectors accordingto the measurement conditions. The optical detector switching controlunit may be configured to power on/off the optical detectors fordetecting light of a wavelength range to be detected under a currentmeasurement condition.

Particularly, since an optical signal with respect to the secondwavelength may need to be detected under both first condition in whichthe excitation light of the first wavelength range is irradiated andsecond condition in which the reflected light of the second wavelengthrange is irradiated, the second optical detector 122 for detecting lightwith respect to the second wavelength may be maintained turned on.

That is, the first optical detectors 121 may be turned on so thatreflected light for the light irradiated from the first light source 111for a first time may be detected, and the second optical detector 122may be turned on so that reflected light for the light irradiated fromthe second light source 112 for a second time after the first time andthe skin fluorescence due to the light irradiated from the first lightsource 111 for the first time may be detected.

In this case, the switching control may be sequentially performed on thelight sources for a certain time during the whole measurement processincluding the first condition and the second condition. In regard to theperiod of switching with respect to each light source, the switchingcontrol may be performed at a high frequency of about 10 Hz to about 10kHz such that the variation of the diffusion reflectance due to theblood flow does not affect the measurement by considering the pulse rateof the human body.

As the measurement scanner 100 of the reflection detection typemeasurement apparatus for skin fluorescence is manufactured in ahand-grippable form, such high-speed switching may achieve measurementon the substantially same target spot even when the measurement scanner100 is moved by a scanning method in which the skin fluorescence iscontinuously measured while the scanner is moving.

Although not shown in FIG. 2, the reflection detection type measurementapparatus for skin fluorescence may include an optical filterselectively disposed at the front of the light source and the opticaldetector. Preferably, in order to prevent the detection of the skinfluorescence with a relatively lower light intensity from becomingdifficult due to specular reflection of irradiated light on the skinsurface, a pair of polarizers 130 and a pair of cross-polarizers 131 maybe disposed between corresponding light sources and optical detectors.

The polarizers and the cross-polarizers may need to be disposed atmutually-crossing locations on a pair of the first light source 111 andthe first optical detector 121 and a pair of the second light source 112and the second optical detector 122, respectively.

Meanwhile, the reflection detection type measurement apparatus for skinfluorescence may be configured to include the main body 200 that isconfigured to be connectable to the measurement scanner 100 includingtwo light sources and two optical detectors. The main body 200 may beconfigured to include an operation part 250 that calculates the value ofcorrected skin fluorescence from data measured by the measurementscanner 100.

The main body 200 may be configured to be optically, electrically andmechanically connectable to the measurement scanner 100.

Specifically, the main body 200 may include a mounting part 210 with ashape matching the shape of a measurement terminal of the measurementscanner 100 such that the measurement scanner 100 can be mechanicallymounted onto the main body 200. The measurement scanner 100 may befixedly mounted into the mounting part 210 through mechanical coupling.

In an exemplary embodiment of the present invention, the first andsecond light sources 111 and 112 and the first and second opticaldetectors 121 and 122 may be configured to be disposed in themeasurement scanner 100, while the mounting part 210 may be configuredto have an aperture formed in a shape corresponding to the shape of oneend portion of the measurement scanner 100, allowing the light sourcesand the optical detectors to be fixed in the mounting part 210 whilefacing each other.

As the measurement scanner 100 is mounted onto the main body 200, themain body 200 may be configured to be electrically connectable to themeasurement scanner 100, allowing the measurement scanner 100 toirradiate light on the measurement target T and acquire data about thedetected skin fluorescence and the reflected light. In addition, areference sample for comparison with the measurement target T may bedisposed on the mounting part 210 of the main body 200, and the lightsources and the optical detectors of the measurement scanner 100 may beconfigured to be optically connected to the reference sample when themeasurement scanner 100 is seated on the mounting part 210 of the mainbody. In this case, the reference sample may be selected so as to havethe optical characteristics of the diffuse reflection and fluorescencesimilar to the human body's tissue that is measured.

Therefore, when the measurement scanner 100 is mounted onto the mountingpart 210 of the main body 200 to be electrically and opticallyconnected, the measurement scanner 100 may perform light irradiation andlight detection processes, which have been performed on the measurementtarget T, on the reference sample. The measured data of the measurementtarget and the reference sample may be transmitted to the operation part250 of the main body 200.

The operation part 250 may calculate corrected skin fluorescence valuesregarding the actual measurement target using data about thefluorescence signals and the reflected light signals that are received.The calculation result may be displayed via the display part 220 on themain body 200.

The above sequential measurement may be repeated. In order to perform anoperation process in which correction is performed according to theresults of the repeated measurement, all measured data may be stored inthe measurement scanner 100 via a memory. Preferably, the measurementresults may be stored in a form of time diagram to trace the variationof the measurement results.

A charging terminal (not shown) may be disposed in the mounting part 210on the main body 200 to charge the measurement scanner 100. The chargingterminal may be configured to perform charging when the measurementscanner 100 is mechanically coupled to the mounting part 210.

If necessary, the measurement scanner 100 may be configured to beconnected to the main body 200 through Bluetooth.

An exemplary arrangement of the light sources and the optical detectorsin the reflection detection type measurement apparatus for skinfluorescence is shown in FIGS. 3 and 4.

FIG. 3 is a view illustrating an exemplary arrangement of light sourcesand optical detectors when there is no gap between the lightsources/optical detectors and the measurement target. FIG. 4 is a viewillustrating an exemplary arrangement of light sources and opticaldetectors when there is a gap between the light sources/opticaldetectors and the measurement target.

As shown in FIG. 3, the light sources and the optical detectors may bedisposed parallel to each other and perpendicular to the measurementtarget, respectively. In order to form an optimum detection region, thefirst light source 111 and the second light source 112 may be disposedat the outer sides, respectively, and the first optical detector 121 andthe second optical detector 122 may be disposed between the first andsecond light sources 111 and 112.

As shown in FIG. 4, when a certain gap exists between the lightsources/optical detectors and the measurement target, the light sourcesand the optical detectors may be obliquely disposed to be inclined withrespect to each other, and may be configured to form light irradiationpaths and light detection paths such that the light sources canirradiate light on the same region of the measurement target and theoptical detectors can detect light generated in the same region,respectively. Preferably, the light source and the optical detectorcorresponding to each other may be disposed to be inclined at an angleof about 45 degrees with respect to each other. For example, when alight source vertically irradiates light on the skin surface, an opticaldetector may be disposed to be inclined at an angle of about 45 degreeswith respect to the light source, thereby reducing an influence ofspecular reflection. An angle between the first and second light sources111 and 112 and the first and second optical detectors 121 and 122 maybe minimized according to the structure of equipment. More preferably,the influence of the specular reflection may be minimized by disposing apair of polarizers 130 and a pair of cross-polarizers 131 betweencorresponding light source and optical detector at the front of thelight sources and the optical detectors together with optical filters toremove the specular reflected light.

In this case, the first light source 111, the second light source 112,the first optical detector 121, and the second optical detector 122 maybe configured to be connected to the end of the measurement target sideof the measurement scanner 100 via a light guide, respectively. Atransparent protection film such as a glass plate may be disposed on thecontact surface between the skin and the sensor to protect themeasurement scanner 100 from foreign substances such as externalmoisture.

Hereinafter, a test example of the light irradiation, the lightdetection, and the operation process performed by the reflectiondetection type measurement apparatus for skin fluorescence configured asabove will be described as follows.

Example 1

It is necessary to perform measurement on a measurement target and areference sample, two targets that are introduced to obtain a correctedfluorescence value. Light measurement is performed on the human body'sskin that is the measurement target among the two targets.

For diagnosis, the measurement is performed by a light source and anoptical detector that contact or get close to the measurement target onthe upper arm of a subject. A measurement scanner moves along the skinsurface to scan the target part of about 5 cm2 to about 19 cm2.

Before the measurement, all light sources are turned off, and then levelevaluation of a dark signal is performed to automatically compensate forlight leaking from the outside. That is, a dark time may be maintainedfor a certain time with respect to the measurement target and a darksignal of the measurement target may be used to compensate the value ofskin fluorescence for a dark time.

A light module sequentially operates light φ(λ1, t1) of first lightsource with a wavelength λ1 and light φ(λ2, t2) of second light sourcewith a wavelength λ2 at different time intervals t1 and t2,respectively.

During the whole measurement process, light generated by two lightsources is sequentially radiated at time intervals t1 and t2 whileswitching on/off is being repeated at a period of about 50 Hz.

Next, light irradiated from the light sources is detected by the opticaldetectors to be converted into electrical signals.

The light φ(λ1, t1) of the first light source of a near-ultravioletspectrum range (near 370 nm) excites the fluorescence of a target toform a corresponding signal I(λ2,t1) by the optical detector, and formsa signal I(λ1,t1) proportional to excitation reflected lightdiffuse-reflected by the skin that is the measurement target.

The light φ(λ2, t2) of the second light source of a blue spectrum range(near 440 nm) corresponds to the maximum value of the inherentfluorescence generated in AGE and NADH, and forms a signal I(λ2,t2)proportional to the reflected light that is diffuse-reflected by thetarget skin.

The above measurement is repeatedly and periodically performed atdifferent time intervals t1 and t2, and the measurement results areaveraged and stored.

The same measurement processes are performed on the reference sample,and data calculated in each process is processed in an operation part tocalculate a corrected skin fluorescence value.

A time diagram regarding the actuation of the light sources having twowavelengths in the above test example may be shown as Table 1 below.

TABLE 1 1st Cycle 2nd Cycle Dark F440/R365 Dark R440 Dark F440/R365 DarkR440 Dark LED365 OFF ON OFF OFF OFF ON OFF OFF OFF LED440 OFF OFF OFF ONOFF OFF OFF ON OFF PD365 ON ON ON OFF ON ON ON OFF ON PD440 ON ON ON ONON ON ON ON ON

In Table 1, the first light source and the second light sourcecorrespond to LED 365, LED 440 respectively, and the first opticaldetector and the second optical detector correspond to PD 365, PD 440respectively

As shown in Table 1, in the skin fluorescence measurement of themeasurement target, a dark time may be maintained for a certain timebefore the light source is turned on at a first step. In this case, thefirst optical detector and the second optical detector may maintain aturned-on state. At a second step, the first light source is turned on.In this case, in a state in which the second optical detector ismaintained to be turned off, the first optical detector and the secondoptical detector may be turned off so as to detect light generated bythe first light source. Thereafter, at a third step, a dark time may bemaintained before the second light source is turned on, and the firstoptical detector and the second optical detector may be still maintainedto be turned off. Finally, at a fourth step, the second light source maybe turned on. In this case, in a state in which the first light sourceis maintained to be turned off, the first optical detector is turned offand the second optical detector is maintained to be turned on. Asdescribed above, throughout the first step to the fourth step, the skinfluorescence value may be measured from the measurement target, and maybe repeatedly performed with a cycle including the first step to thefourth step.

In this test example, the respective cycle time is configured to beabout 20 ms. Also, the measurement target scanning time is calculated asabout 2 seconds, and 100 measurement cycles are performed.

Data measured in this test example is stored and preserved in aninternal memory of the measurement scanner. When the measurement scanneris placed on the mounting part of the main body, the detectioninformation is automatically moved to the operation part of the mainbody to undergo an operation according to function conversion and bestatistically processed, and the measurement results are displayed.

Meanwhile, the present invention proposes a structure in which anoptical prism and an optical connector are disposed on an optical pathsuch that the optical transmission and detection efficiencies can beimproved.

FIG. 5 illustrates a reflection detection type measurement apparatus forskin fluorescence according to an embodiment of the present invention,compared with a typical reflection detection type measurement apparatusfor skin fluorescence. FIG. 5A illustrates the optical irradiation andthe optical detection without an optical prism and an opticalconnection. FIG. 5B illustrates the optical irradiation and the opticaldetection with an optical prism and an optical connection.

In a case where the optical irradiation and the optical detection areperformed without an optical prism and an optical connector as shown inFIG. 5A, excitation light may be irradiated from a light source 310, andthen an optical detector 320 may detect fluorescence caused by theexcitation light.

In this case, as shown in FIG. 5A, since the light source 310 such as aLight Emitting Diode (LED) used as an excitation light source irradiateslight with a wide divergence angle, an optical loss may occur on ameasurement target, and scattering of fluorescence from the skin onwhich light is irradiated may cause a loss of the quantity of lightdetected by the optical detector 320.

Since the skin fluorescence detected is significantly smaller than otherexcitation light or reflected light thereof, the optical loss mayconsiderably reduce the accuracy of the measurement and the reliabilityof the diagnosis even when the optical loss is slight.

On the other hand, in order to prevent the optical loss, a reflectiondetection type measurement apparatus for skin fluorescence including anoptical prism is proposed as shown in FIG. 5B.

Referring to FIG. 5B, the excitation light irradiated from the lightsource 310 may be concentrated by the optical prism 330, and the opticaluniformity of a skin part that is the measurement target can beimproved.

Specifically, the optical prism 330 may have two upper inclinationsurfaces 331 and 332 that are adjacent to the light source 310 and theoptical detector 320, respectively, and a lower surface 333 that isadjacent to the skin. Excitation light irradiated from the upperinclination surface 331 adjacent to the light source 310 with a widedivergent angle may be totally reflected from the inside of the upperinclination surface 332 of the optical prism 330 at the side of theoptical detector 320 may be maximally concentrated on the skin, therebyreducing the non-uniformity of the light source, i.e., thecharacteristics in which the optical intensity becomes smaller at theouter side of the optical axis than at the center of the optical axisand thus achieving improved optical uniformity.

Also, the optical prism 330 may serve to concentrate a secondary lightgenerated by light transmitted to the skin tissue part on the opticaldetector 320. Accordingly, in the reflection detection type measurementapparatus for skin fluorescence, an optical signal can be improved, anda measurement error can be reduced. Thus, an optical measurement can beperformed on a wide skin part without a scanning method of an opticalsensor.

The reflection detection type measurement apparatus for skinfluorescence according to the embodiment of the present invention may beconfigured to include an optical connector 340 for reducing a specularreflection component reflected by the surface of the skin that is themeasurement target and allowing light to effectively penetrate into theskin.

The optical connector 340 may be configured to locate between theundersurface 333 of the optical prism 330 adjacent to the skin that isthe measurement target and the surface of the skin, and may contact theundersurface 333 of the optical prism and the surface of the skin,respectively.

The optical connector 340 may contact the undersurface 333 of theoptical prism 330 and the surface of the skin to serve as a connectionlayer for allowing a smooth optical contact with an appropriaterefractive index at the boundaries thereof. The optical connector 340may prevent the specular reflection from the surface of the skin, andmay allow light to effectively penetrate into the skin.

The optical connector 340 may have a certain refractive index betweentwo media to prevent a light leakage that may occur between the twomedia due to the refraction and scattering of the excitation lightbetween the optical prism 330 and the skin tissue, and may serve to filluneven portions such as fine unevenness of the skin tissue.

The optical connector 340 may be formed of an elastic material or aliquid material such as water or oil-immersion. The optical connector340 may be formed of a material having a refractive index similar tothose of the optical prism 330 and the skin.

Due to the optical connector 340, the total internal reflection of theirradiated light may not occur at the boundaries between the prism andthe skin tissue, and the penetration efficiency of light emitting fromthe light source into the skin can be significantly improved.

Accordingly, the reflection detection type measurement apparatus forskin fluorescence including the optical prism 330 and the opticalconnector 340 can improve the optical concentration and the opticaluniformity, and can significantly reduce the specular reflectioncomponent of light irradiated from the light source by the surface ofthe skin.

Example 2

A reflection detection type measurement apparatus for skin fluorescenceincluding an optical prism and an optical connector was manufactured.Also, as a comparative example, an apparatus configured such that alight source and an optical detector are located similarly to those ofthe reflection detection type measurement apparatus and opticalirradiation and optical detection are performed without the opticalprism and the optical connector was manufactured.

In this test example, a UV LED (No 33, Nichia) emitting light of about365 nm was used as the light source, and an optical fiber spectrometer(AVaspec-2048) was used as the optical detector. Also, an opticalphotodiode may also be used as the optical detector. A commercializedmodel (Right Angle Prism, Uncoated, 20 mm, Edmund Optics) was used asthe optical prism.

In this test example, water was used as the optical connector, which wasinterposed between the optical prism and the surface of the skin that isthe measurement target.

A specular reflection component of light irradiated from the lightsource in the reflection detection type measurement apparatus of thetest example was measured, and a specular reflection component in theapparatus of the comparative example was also measured.

In the measurement results from the test example and the comparativeexample, the specular reflection component of the test example wasmeasured to be reduced by about ten times or more compared to that ofthe comparative example.

FIG. 6 illustrates a reflection detection type measurement apparatus forskin fluorescence including two light sources 311 and 312 and twooptical detectors 321 and 322, which is configured as shown in the testexamples 1 and 2. Like in FIG. 5, an optical prism 330 and an opticalconnector 340 may be interposed between the two light sources 311 and312 and the two optical detectors 321 and 322 and the skin T that is themeasurement target.

In this embodiment, the optical prism 330 may have two upper inclinationsurfaces 331 and 332 adjacent to the light source and the opticaldetector, respectively, and a lower surface 333 adjacent to the skin. Atriangular prism 330 333 having a triangular section may be used like inFIG. 5. Preferably, the two light sources 311 and 312 may be disposed onthe upper inclination surface 331 of the triangular prism 330, and thetwo optical detectors 321 and 322 may be disposed on the upperinclination surface 332 of the triangular prism, allowing theundersurface 333 of the prism 330 to contact the skin.

In this case, when the two different light sources 311 and 312 aredisposed on the upper inclination surface 331, the optical axes of thetwo light sources 311 and 312 may differ from each other. Accordingly,the regions of the skin T on which the light is irradiated may differfrom each other.

However, since the light source is connected to the measurement target Tthrough the optical prism 330, uniform light in which the differencebetween the optical axes can be corrected by the optical reflectioninside the optical prism 330 can be obtained.

Also, a polarizer 351 may be disposed between the light sources 311 and312 and the optical prism 330, and a cross polarizer 352 may be disposedbetween the optical detectors 321 and 322 and the optical prism 330. Asshown in FIG. 6, the polarizer 351 may be disposed on the upperinclination surface of the optical prism 330 under the first and secondlight sources 311 and 312, and the cross polarizer 352 may be disposedon the other upper inclination surface of the optical prism 330 underthe first and second optical detectors 321 and 322.

As shown in FIG. 6, the optical connector 340 may be disposed betweenthe skin T that is the measurement target and the undersurface 333 ofthe optical prism 330. The optical connector 340 may contact theundersurface 333 of the optical prism 330 and the surface of the skin T,respectively, allowing smooth optical contact with an appropriaterefractive index at the boundaries thereof.

Accordingly, the specular reflection component generated from thesurface of the skin T by the optical connector 340 can be reduced, andlight partially reflected by a difference of the refractive indexbetween the surface of the skin T and the optical connector 340 can beadditionally inhibited by the cross polarizer 352 disposed at the frontof the optical detectors 321 and 322.

The reflection detection type measurement apparatus for skinfluorescence may be configured to be connected to a main body 360 thatincludes a light source switching controller for controlling turningon/off of the first and second light source 311 and 312 and an operatorfor calculating a correction value of a skin fluorescence signal from adetected fluorescence signal and a reflected light signal.

As described in FIG. 2, in the reflection detection type measurementapparatus for skin fluorescence according to this embodiment, the lightsource 311 and 312 and the optical detectors 321 and 322 may also bedisposed at one end of a measurement scanner, and a corrected skinfluorescence value can be obtained by an operation process similar tothat of FIG. 2 except that the light irradiation is performed throughthe optical prism disposed between the light source and the measurementtarget.

FIG. 7 illustrates a reflection detection type measurement apparatus forskin fluorescence according to another embodiment of the presentinvention. As shown in FIG. 7, the reflection detection type measurementapparatus may include an optical prism 430 of a trapezoidal sectionhaving an upper surface 431, a lower surface 432, and two inclinationsurfaces 433 and 434, and an optical connector 440 interposed betweenthe lower surface 432 and the skin T. Two light sources 411 and 412 maybe disposed over the two inclination surface 433 and 434, respectively,and two optical detectors 421 and 422 may be disposed over the uppersurface 431 of the optical prism 430.

Unlike FIG. 6, the optical prism 430 may have a trapezoidal section,which further has the upper surface in addition to the two upperinclination surfaces and the undersurface.

Specifically, the optical prism 430 may be formed to have a trapezoidalshape in which the upper surface 431 is further included in addition tothe two upper inclination surfaces 433 and 434 adjacent to the lightsource and the optical detector, respectively, and the lower surface 432adjacent to the skin T. Also, the light sources 411 and 412 and theoptical detectors 421 and 422 may be disposed over the two upperinclination surfaces 433 and 434 and the upper surface 431,respectively.

In this embodiment, the first light source 411 and the second lightsource 412 irradiating light having a wavelength different from thefirst light source 411 may be disposed over the upper inclinationsurfaces 433 and 434 of the optical prism 430, respectively. Also, thefirst and second optical detectors 421 and 422 may be disposed over theupper surface 431 connected to the two upper inclination surfaces 433and 434 to detect light having different wavelengths regarding afluorescence signal and a reflected light signal.

Similarly to FIG. 6, a polarizer 451 and a cross polarizer 452 may bedisposed between the light source 411 and 412 or the optical detectors421 and 422 and the optical prism 430 to remove reflected light,respectively. As shown in FIG. 7, the polarizer 451 may be disposedbetween the first and second light source 411 and 412 and the upperinclination surfaces 433 and 434 of the optical prism 430, and the crosspolarizer 452 may be disposed between the first and second opticaldetector 421 and 422 and the upper inclination surface 431 of theoptical prism 430.

Also, an optical connector 440 may be disposed between the undersurface432 of the optical prism 430 and the skin T that is the measurementtarget. The optical connector 440 may contact the undersurface 432 ofthe optical prism 430 and the surface of the skin T, respectively.

FIGS. 8 and 9 illustrate reflection detection type measurementapparatuses for skin fluorescence according to other embodiments of thepresent invention. In these embodiments, optical prisms havingtrapezoidal sections may be used similarly to that of FIG. 7, but thearrangement of light sources and optical detectors is different fromeach other.

In FIG. 8, two light sources 411 and 412 may be disposed over the uppersurface 431 of an optical prism 430, and two optical detectors 421 and422 may be disposed over two upper inclination surfaces 433 and 434,respectively.

In FIG. 9, two light sources 411 and 412 may be disposed over one upperinclination surface 433 of an optical prism 430, and two opticaldetectors 421 and 422 may be disposed over the other upper inclinationsurface 434 of the optical prism 430.

FIG. 10 illustrates a reflection detection type measurement apparatusfor skin fluorescence according to another embodiment of the presentinvention. In this embodiment, an optical prism 430 of a trapezoidalsection having four upper inclination surfaces 433, 434, 435 and 436 maybe disposed. Here, two light sources 411 and 412 and two opticaldetectors 421 and 422 may be disposed over the upper inclinationsurfaces 433, 434, 435 and 436 such that the two light sources 411 and412 and the two optical detectors 421 and 422 face each other,respectively.

As shown in FIG. 10, the first light source 411 and the second lightsource 412 may be selectively disposed over the two upper inclinationsurfaces 435 and 436, and the first optical detector 421 and the secondoptical detector 422 may be selectively disposed over the other twoupper inclination surfaces 433 and 434.

The first and second light sources 411 and 412 may be disposed over thetwo upper inclination surfaces 435 and 436 that are opposite to eachother, and the first optical detector 421 and the second opticaldetector 422 may be disposed over the two upper inclination surfaces 433and 434 that are opposite to each other.

In this case, the light sources 411 and 412 and the optical detectors421 and 422 may be disposed orthogonally to each other. Such theorthogonal arrangement may reduce a specular reflection component.

A reflection detection type measurement apparatus for skin fluorescenceaccording to an embodiment of the present invention may include a holderto which the first light source 411, the second light source 412, thefirst optical detector 421, and the second optical detector 422 areinserted to be disposed to face the same area of the measurement target.Such the holder may have a specific shape, for a typical example, ashape of pyramid, so as to measure the light generated from themeasurement target due to the light irradiated from the first and secondlight sources.

A reflection detection type measurement apparatus for skin fluorescenceaccording to an embodiment of the present invention may be configured tohave a structure in which two light sources 111 and 112 and two opticaldetectors 121 and 122 are disposed at four sides of such a holder,respectively. The measurement principle of the pyramidal measurementapparatus for skin fluorescence may be substantially similar to the casewhere the light source and the optical detector are disposed side byside as shown in FIG. 1.

In this regard, FIG. 11 illustrates a pyramidal holder equipped with twolight sources and two optical detectors, and FIG. 12 is a plan viewillustrating the pyramidal holder.

As shown in FIG. 11, a reflection detection type measurement apparatusfor skin fluorescence according to an embodiment of the presentinvention may include a measurement scanner 100 that can irradiateexcitation light and detect skin fluorescence and a main body 200 thatis connected to the scanner 100 to analyze information detected from thescanner and display the information.

However, this configuration in which the measurement scanner 100 and themain body 200 are separately provided is merely one of exemplaryembodiments of the present invention, Accordingly, a separate main bodymay not be provided according to a need, but may be manufactured in asingle sensor type, and other components may be additionally connectedthereto.

The light source and the optical detector may be disposed on a pyramidalmeasurement module 500 disposed on one end of the measurement scanner100.

That is, the two light sources and the two optical detectors may bemounted in the four side surfaces of the pyramidal holder to form thepyramidal measurement module 500 disposed on one end of the measurementscanner 100 as shown in FIG. 11.

More specifically, as shown in FIG. 12, the pyramidal holderconstituting the pyramidal measurement module 500 may have fourthrough-holes in four side surfaces thereof, and the four through-holesmay receive the light sources L1 and L2 and the optical detectors D1 andD2, respectively.

In this case, as shown in FIG. 12, the light sources L1 and L2 may bemounted in two side surfaces of the pyramidal holder opposite to eachother with respect to different wavelengths, respectively, and theoptical detectors D1 and D2 are mounted in the other two side surfacesof the pyramidal holder opposite to each other with respect to differentwavelengths, respectively.

In this arrangement, when considering the irradiation angle of light andthe main optical path of the reflected light according thereto, thedirect inflow of reflected light to the optical detector may reduce.

FIGS. 13 through 15 illustrate the concrete configuration of a pyramidalmeasurement module 500 of a reflection detection pyramidal measurementapparatus for skin fluorescence according to an embodiment of thepresent invention.

FIG. 13 is an exploded perspective view of a pyramidal measurementmodule according to an embodiment of the present invention. FIGS. 14 and15 are side views when viewed from arrows “A” and “B” of FIG. 13.

As shown in FIG. 13, the pyramidal module 500 of the reflectiondetection pyramidal measurement apparatus for skin fluorescence mayinclude two light sources and two optical detectors, and a pyramidalholder 530 equipped with the light sources and the optical detectors.

The pyramidal holder 530 may have a pyramidal shape having four sidesurfaces and one bottom surface. The light sources and the opticaldetectors may be installed in the side surfaces of the pyramidal holder530, respectively.

More specifically, four through-holes 531, 532, 533 and 534 may beformed in the side surface of the pyramidal holder 530 to receive thelight sources and the optical detectors. That is, as shown in FIG. 12,the first through-hole 531 formed in one side surface of the pyramidalhold 530 may receive the first light source 511, and the secondthrough-hole 532 opposite thereto may receive the second light source512. Also, the third through-hole 533 and the fourth through-hole 534may be formed in the two side surfaces between the two side surfaceshaving the first through-hole 531 and the second through-hole 532,respectively. The third through-hole 533 may receive the first opticaldetector 513 and the fourth through-hole 534 may receive the secondoptical detector 514.

In this case, the two light sources may be disposed so as to obliquelyirradiate light from the side surfaces of the pyramidal holder 530 to ameasurement target. The two optical detectors may also be obliquelydisposed on the two side surfaces opposite to each other.

Also, optical irradiation paths and optical detection paths may beallowed to be formed such that the light sources and the opticaldetectors can irradiate light on the same region of the measurementtarget and detect light generated from the same region. Preferably,light sources and the optical detectors opposite to each other may beobliquely disposed at an angle of about 45 degrees with respect to thebottom surface of the pyramidal holder 530 adjacent to the measurementtarget, thereby significantly reducing an influence of the specularreflection.

Also, a pair of polarizers 515 and 516 and cross polarizers 517 and 518may be disposed in the through-holes 531, 532, 533 and 534 together withoptical filters 519 and 520 to minimize the influence of the specularreflection.

That is, the pyramidal holder 530 may be provided with a stepped partinside of the through-hole so as to store optical component such aspolarizer, cross polarizer, and optical filter.

The polarizers 515 and 516, the cross polarizers 517 and 518, and theoptical filters 519 and 520 may be disposed in the through-holes 531,532, 533 and 534 so as to be adjacent to the bottom surface of thepyramidal holder 530 at the inner side of the light sources and theoptical detectors.

The through-holes 531, 532, 533 and 534 formed in the four side surfacesof the pyramidal holder 530 may communicate with the center, and may beconnected to the opening (535) of the bottom surface of the pyramidalholder 530.

A window 525 may be formed in the opening 535 to contact the measurementtarget, and the window 525 may be selected in consideration of therefractive index of light, and may be formed of a transparent materialsuch as glass.

The window 525 may serve to protect surfaces contacting the skin and thesensor from foreign substances such as external humidity.

Also, a bottom plate 526 may be coupled to the bottom surface of thepyramidal holder 530 via a coupling member such as a bolt 527 to fix thewindow 525. The bottom plate 526 may have an opening at the centerthereof such that the window 525 can be disposed.

Although not shown, the reflection detection type measurement apparatusfor skin fluorescence may further include an optical connector thatreduces a specular reflection component reflected from the skin surfacethat is a measurement target and allows light to effectively penetrateinto the skin.

The optical connector may be configured to locate between the skinsurface and the window 525 adjacent to the skin that is the measurementtarget and contact the window 525 and the skin surface, respectively.

Preferably, a step may be formed between the bottom of the bottom plate526 and the undersurface of the window 525. The optical connector may befilled in the portion where the step is formed to form a structure inwhich the optical connector is contactable with the measurement target.

Accordingly, the optical connector may contact the window 525 and thesurface of the skin to serve as a connection layer for enabling a smoothoptical contact with an appropriate refractive index at the boundariesthereof. The optical connector may prevent the specular reflection fromthe surface of the skin, and may allow light to effectively penetrateinto the skin.

The optical connector may have a certain refractive index between twomedia to prevent a light leakage that may occur between two media due tothe refraction and scattering of the excitation light between the window525 and the skin tissue, and may serve to fill uneven portions such asfine unevenness of the skin tissue.

The optical connector may be formed of an elastic material or a liquidmaterial such as water or oil-immersion. Also, the optical connector maybe formed of a material having a refractive index similar to those ofthe window 525 and the skin.

Meanwhile, mounting grooves may be formed in the through-holes 531, 532,533 and 534 of the pyramidal holder 530 such that the light sources, theoptical detectors, the polarizers, the cross polarizers, and the opticalfilters can be seated in the appropriate positions, respectively.

In FIG. 13, four side plates 521, 522, 523 and 524 may be fixedlymounted on the side surfaces of the pyramidal holder 530, and the lightsources and the optical detectors may be mounted on the side plates 521,522, 523 and 524. That is, the two light sources may be mounted at theinner side of the two side plates among the four side plates 521, 522,523 and 524, and the two optical detectors may be mounted at the innerside of the other two side plates. The side plates 521, 522, 523 and 524may be fixed on the pyramidal holder 530 by a coupling member such asthe bolt 527.

Similarly to that described above, in FIG. 13, the optical irradiationfrom the light source to the measurement target and the opticaldetection of a fluorescence signal may be performed through the fourthrough-holes 531, 532, 533 and 534.

The side views when viewed from the arrows “A” and “B” of FIG. 13 areshown in FIGS. 14 and 15. In FIGS. 14 and 15, the arrangement of thelight sources, the optical detectors, the polarizers, and the opticalfilters are shown.

Hereinafter, an exemplary embodiment of the optical radiation, theoptical detection, and the operation process performed by the reflectiondetection type measurement apparatus for skin fluorescence will bedescribed as follows.

Example 3

It is necessary to perform measurement on a measurement target and areference sample, two targets that are introduced to obtain a correctedfluorescence value. Light measurement is performed on the human body'sskin that is the measurement target.

For diagnosis, the measurement is performed by a light source and anoptical detector that contact or get close to the measurement target onthe upper arm of a subject. A measurement scanner moves and scans alongthe skin surface to scan the target area of about 5 cm² to about 19 cm².The optical irradiation area of the reflection detection type pyramidalmeasurement apparatus for skin fluorescence may be about 15 mm indiameter at a time.

Before the measurement, all light sources are turned off, and then levelevaluation of a dark signal is performed to automatically compensate forlight leaking from the outside.

A light module sequentially generates first light source illuminationlight φ(λ1, t1) with a wavelength λ1 and second light sourceillumination light φ(λ2, t2) with a wavelength λ2 at different timeintervals t1 and t2, respectively.

During the whole measurement process, light generated by two lightsources is sequentially radiated at time intervals t1 and t2 whileswitching on/off is being repeated at a period of about 50 Hz.

Next, light irradiated from the light sources is detected by the opticaldetectors to be converted into electrical signals.

The first light source illumination light φ(λ1, t1) of anear-ultraviolet spectrum range (near 370 nm) excites the fluorescenceof a target to form a corresponding signal I(λ2, t1) by the opticaldetector, and forms a signal I(λ1,t1) proportional to excitationreflected light diffuse-reflected by the skin that is the measurementtarget. For the test, the first optical detector 513 for measuring areflected light single value of the target skin tissue in the excitationlight wavelength used a 370 nm±20 nm UV bandpass filter as the opticalfilter 519, and a product #48-630 from Edmund Optics Inc was used.

The second light source illumination light φ(λ2, t2) of a blue spectrumrange (near 440 nm) corresponds to the maximum value of the inherentfluorescence generated in AGE and NADH, and forms a signal I(λ2,t2)proportional to the emission light that is diffuse-reflected by thetarget skin. The second optical detector 514 for measuring an inherentfluorescence signal value of the skin tissue used a 440 nm±20 bandpassfilter as the optical filter 520, and a product #86-340 from EdmundOptics Inc was used. In the second optical detector 514, a bandpassfilter 520 as described above was used to transmit the inherentfluorescence of the skin tissue and interrupt the wavelength of theexcitation light, i.e., about 370 nm reflected from the skin tissue.

The above measurement is repeatedly and periodically performed atdifferent time intervals t1 and t2, and the measurement results areaveraged and stored.

The same measurement processes are performed on the reference sample,and data calculated in each process is processed in an operation part tocalculate a corrected skin fluorescence value.

Meanwhile, in order to obtain the corrected fluorescence signal value ofthe skin tissue, reflected lights reflected by the measurement targetfrom the first light source 511 and the second light source 512 emittinglight having a fluorescence wavelength have to be detected. However,since the intensity of the reflected light is relatively larger than theintensity of the inherent fluorescence emitted from the skin tissue,measurement signal saturation may occur in the first and second opticaldetectors upon detection of the reflected lights. Accordingly, in orderfor the optical detectors to simultaneously detect the reflected lightsand the inherent fluorescence value without a loss, optical attenuationfilters that reduce the amount of light within an irradiation range anddo not generate fluorescence in a visible light range may be disposed ona portion of optical paths.

In this regard, FIG. 16 illustrates optical attenuation filters disposedat the front of the second light source and the first optical detector.In this embodiment, optical attenuation filters 536 and 537 may bedisposed at the front of the second light source 512 and the firstoptical detector 513, and the optical attenuation filter may not bedisposed at the first light source 511 and the second optical detector514. That is, as shown in FIG. 16A, the optical attenuation filter 536may be disposed at the front of the first optical detector 513, and asshown in FIG. 16B, the other optical attenuation filter 537 may bedisposed at the front of the second light source.

Thus, the optical attenuation filters 536 and 537 can prevent saturationof the signal output in the first and second optical detectors 513 and514 by lowering the intensity of the reflected light of the excitationlight and the emission light. On the other hand, since the opticalattenuation filter is not disposed at the front of the first lightsource 511 that excites the inherent fluorescence and the second opticaldetector 514 that detects the fluorescence signal, the fluorescencesignal value can be detected without a loss.

As described above, a reflection detection type measurement apparatusfor skin fluorescence according to an embodiment of the presentinvention has the following advantages.

First, in an embodiment of the present invention, since diabeticdiseases can be easily diagnosed by evaluating the skinautofluorescence, mass inspection can be performed to find potentialdiabetic patients. In addition, the risk of cardiac-vascular diseasesand complications thereof can be predicted.

Second, in an embodiment of the present invention, since the opticalconcentration and the optical uniformity of light irradiated from alight source are improved, more uniform light can be irradiated on themeasurement target.

Third, in an embodiment of the present invention, since the opticalefficiency can be improved by efficiently concentrating light from alight source on the skin tissue and minimizing the specular reflectionon the surface of the skin tissue, the miniaturization of the apparatuscan be achieved.

Fourth, in an embodiment of the present invention, since an error due tospecular reflection generated on the skin surface and an error due tolight scattering and absorption generated inside the skin can becorrected in measuring skin fluorescence, exact measurement of the skinfluorescence and exact diagnosis of diseases using the skin fluorescencecan be achieved.

Fifth, in an embodiment of the present invention, the reflectiondetection type measurement apparatus for skin fluorescence may includelight sources and optical detectors, and may be manufactured in a formof hand-grippable small-size scanner to measure the skin fluorescence.Thus, since a user can scan a diagnostic target by contacting thescanner with the skin of a subject, non-invasive diagnosis can beperformed in real-time.

Sixth, in an embodiment of the present invention, since a selectivediagnosis is enabled on certain body parts, and the area of themeasurement target can be extended to a certain extent through thescanning method, the reliability of a signal and the accuracy ofdiagnosis can be improved.

The invention has been described in detail with reference to exemplaryembodiments thereof. However, it will be appreciated by those skilled inthe art that changes may be made in these embodiments without departingfrom the principles and spirit of the invention, the scope of which isdefined in the appended claims and their equivalents.

What is claimed is:
 1. A reflection detection type measurement methodfor skin fluorescence, the method comprising: irradiating excitationlight on a measurement target; detecting a reflected light and a skinfluorescence generated from the measurement target due to the excitationlight; irradiating light with a wavelength range of the skinfluorescence on the measurement target; detecting a reflected lightgenerated from the measurement target due to the light with a wavelengthrange of the skin fluorescence; and calculating a skin fluorescencevalue of the measurement target by correcting a calculation based on thedetected reflected light and skin fluorescence.
 2. The reflectiondetection type measurement method of claim 1, wherein a dark time ismaintained for a certain time before irradiating the excitation light onthe measurement target, and a dark signal value of the measurementtarget compensates the skin fluorescence value during the dark time. 3.The reflection detection type measurement method of claim 1, wherein awavelength of the excitation light has a range of 370±20 nm.
 4. Thereflection detection type measurement method of claim 1, wherein awavelength of the skin fluorescence has a range of 440±20 nm.
 5. Thereflection detection type measurement method of claim 1, wherein theexcitation light and the skin fluorescence are irradiated on the samearea of the measurement target.
 6. The reflection detection typemeasurement method of claim 1, wherein the excitation light isirradiated on the measurement target for a first time, and the skinfluorescence is irradiated on the measurement target for a second timeafter the first time.
 7. The reflection detection type measurementmethod of claim 1, wherein detecting a reflected light and a skinfluorescence generated from the measurement target due to the excitationlight comprises detecting light with a specific wavelength range of thereflected light and the skin fluorescence.
 8. The reflection detectiontype measurement method of claim 7, wherein a wavelength range of thereflected light is smaller than a wavelength range of the skinfluorescence.
 9. A reflection detection type measurement method for skinfluorescence, the method comprising: detecting light with a firstwavelength range and light with a second wavelength range generated froma measurement target by irradiating the light with a first wavelengthrange on the measurement target; detecting the light with a secondwavelength range generated from the measurement target by irradiatingthe light with a second wavelength range on the measurement target; andcalculating a skin fluorescence value of the measurement target bycorrecting a calculation based on the detected light with a firstwavelength range and light with a second wavelength range.
 10. Thereflection detection type measurement method of claim 9, furthercomprising maintaining a certain dark time before irradiating the lightwith a first wavelength range on the measurement target.
 11. Thereflection detection type measurement method of claim 9, furthercomprising maintaining a certain dark time before irradiating the lightwith a second wavelength range on the measurement target.
 12. Areflection detection type measurement apparatus for skin fluorescence,the apparatus comprising: a first light source irradiating light with afirst wavelength range on a measurement target; a second light sourceirradiating light with a second wavelength range on the measurementtarget; a first optical detector detecting the light with a firstwavelength range generated from the measurement target by the light ofthe first light source; a second optical detector detecting the lightwith a first wavelength range generated from the measurement target bythe light of the first light source, and detecting the light with asecond wavelength range generated from the measurement target by thelight of the second light source; and a light source switchingcontroller controlling a turned on/off of the first light source and thesecond light source.
 13. The reflection detection type measurementapparatus of claim 12, wherein the light with a second wavelength rangeis longer than the light with a first wavelength range.
 14. Thereflection detection type measurement apparatus of claim 12, wherein thelight source switching controller turns off the first light source andthe second light source so as to maintain a dark time for a certain timebefore irradiating the light of the first light source.
 15. Thereflection detection type measurement apparatus of claim 12, wherein thelight source switching controller turns off the first light source andthe second light source so as to maintain a dark time for a certain timebefore irradiating the light of the second light source.
 16. Thereflection detection type measurement apparatus of claim 12, wherein thefirst optical detector is turned off while the second optical detectordetects the light generated from the measurement target due to the lightwith a second wavelength range.
 17. The reflection detection typemeasurement apparatus of claim 14, wherein the first optical detectorand the second optical detector are turned on during a dark timemaintained for a certain time before irradiating the light of the firstlight source.
 18. The reflection detection type measurement apparatus ofclaim 15, wherein the first optical detector and the second opticaldetector are turned on during a dark time maintained for a certain timebefore irradiating the light of the second light source.
 19. Thereflection detection type measurement apparatus of claim 12, wherein thefirst wavelength range has a range of 370±20 nm.
 20. The reflectiondetection type measurement apparatus of claim 12, wherein the secondwavelength range has a range of 440±20 nm.